PROSITE documentation PDOC51537
Norovirus 3C-like protease (NV 3CLpro) domain profile


Noroviruses (NVs; formerly "Norwalk-like viruses") [E1], which belong to the Caliciviridae, are the major causative agents of nonbacterial acute gastroenteritis in humans. The NV genome, which consists of positive-sense, single-stranded RNA, contains three open reading frames (ORFs). The first ORF produces a polyprotein that is processed by the viral 3C-like protease into six nonstructural proteins. The six NV ORF1 nonstructural proteins are homologous to picornaviral nonstructural proteins and are named accordingly: N-terminal protein, 2C-like nucleoside triphosphatase, 3A-like protein, 3B VPg (genome-linked viral protein, 3C-like protease (NV 3CLpro), and a 3D RNA-dependent RNA polymerase. NV 3CLpros are the key enzymes for ORF1 polyprotein processing and also cleave the poly(A)-binding protein, causing cellular translation inhibition. NV 3CLpros belong to the chymotrypsin-like protease family, in that they appear to have chymotrypsin-like folds. Whether the 3CLpro domain has a catalytic dyad of composed of histidine and cysteine or tryad of histidine, glutamate and cysteine remains controversial [1,2]. The NV 3CLpro domain forms peptidase family C37 [E2].

The NV 3CLpro domain adopts a serine protease-like fold that consists of two β-barrels separated by a cleft within which lie the active site catalytic residues (see <PDB:1WQS>). The N-terminal β barrel has two α-helices and seven β-strands. The β-strands form a twisted antiparallel β-sheet ressembling an incomplete β-barrel. The core of the incomplete β-barrel contains hydrophobic residues. The active site histidine residue is found in the N-terminal β-barrel, as well as the glutamate. The C-terminal six-stranded antiparallel β-barrel contains the active site cysteine. The catalytic site formed is situated deep within a cleft between the N- and C-terminal β-barrels [1,2].

The profile we developed covers the entire NV 3CLpro domain.

Last update:

May 2011 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

NV_3CL_PRO, PS51537; Norovirus 3C-like protease (NV 3CLpro) domain profile  (MATRIX)


1AuthorsNakamura K. Someya Y. Kumasaka T. Ueno G. Yamamoto M. Sato T. Takeda N. Miyamura T. Tanaka N.
TitleA norovirus protease structure provides insights into active and substrate binding site integrity.
SourceJ. Virol. 79:13685-13693(2005).
PubMed ID16227288

2AuthorsZeitler C.E. Estes M.K. Venkataram Prasad B.V.
TitleX-ray crystallographic structure of the Norwalk virus protease at 1.5-A resolution.
SourceJ. Virol. 80:5050-5058(2006).
PubMed ID16641296



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